Indium(III) complexes with lapachol: cytotoxic effects against human breast tumor cells and interactions with DNA.

Autor: de Carvalho AB; Departamento de Química, Universidade Federal de Minas Gerais, 31.270-901, Belo Horizonte, Minas Gerais, Brazil., Souza AMS; Departamento de Química, Universidade Federal de Minas Gerais, 31.270-901, Belo Horizonte, Minas Gerais, Brazil., Bento LP; Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31.270-901, Belo Horizonte, Minas Gerais, Brazil., de Oliveira Silva M; Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31.270-901, Belo Horizonte, Minas Gerais, Brazil., Souza-Fagundes EM; Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31.270-901, Belo Horizonte, Minas Gerais, Brazil., Diniz R; Departamento de Química, Universidade Federal de Minas Gerais, 31.270-901, Belo Horizonte, Minas Gerais, Brazil., Beraldo H; Departamento de Química, Universidade Federal de Minas Gerais, 31.270-901, Belo Horizonte, Minas Gerais, Brazil. hberaldo@ufmg.br.
Jazyk: angličtina
Zdroj: Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry [J Biol Inorg Chem] 2024 Aug; Vol. 29 (5), pp. 519-529. Date of Electronic Publication: 2024 Jul 16.
DOI: 10.1007/s00775-024-02062-0
Abstrakt: Lapachol (2-hydroxy-3-(3-methylbut-2-en-1-yl)naphthalene-1,4-dione) is a 1,4-naphthoquinone-derived natural product that presents numerous bioactivities and was shown to have cytotoxic effects against several human tumor cells. Indium(III) complexes with a variety of ligands also exhibit antineoplastic activity. Indium(III) complexes [In(lap)Cl 2 ].4H 2 O (1), [In(lap) 2 Cl(Et 3 N)] (2), [In(lap) 3 ]·2H 2 O (3) [In(lap)(bipy)Cl 2 ] bipy = 2,2'-bipyridine (4) and [In(lap)(phen)Cl 2 ] phen = 1,10-phenanthroline (5) were obtained with 2-hydroxy-3-(3-methylbut-2-en-1-yl)naphthalene-1,4-dione (lapachol). Crystal structure determinations for (4) and (5) revealed that the indium(III) center is coordinated to two O atoms from lapachol, two N atoms from 1,10-phenanthroline or 2,2'-bipyridine, and two chloride anions, in a distorted octahedral geometry. Although both complexes (4) and (5) interacted with CT-DNA in vitro by an intercalative mode, only 5 exhibited cytotoxicity against MCF-7 and MDA-MB breast tumor cells. 1,10-phenanthroline and complex (5) presented cytotoxic effects against MCF-7 and MDA-MB cells, with complex (5) being threefold more active than 1,10-phenanthroline on MCF-7 cells. In addition, complex (5) significantly reduced the formation of MDA-MB-231 colonies in a clonogenicity assay. The foregoing results suggest that further studies on the cytotoxic effects and cellular targets of complex (5) are of utmost relevance.
(© 2024. The Author(s), under exclusive licence to Society for Biological Inorganic Chemistry (SBIC).)
Databáze: MEDLINE
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